PURPOSE: Cardiac myxoma, the most common primary tumor of the heart, has variable clinical presentations and variable immunohistochemical profiles. The existence of apoptosis in cardiac myxoma has been demonstrated. The purpose of this investigation was to elucidate the pathway of apoptosis and the cell cycle in cardiac myxomas.
METHODS: This study had two parts: investigation of a cultured cardiac myxoma cell line and the analysis of data from 20 patients with cardiac myxoma that was surgically excised. Apoptosis signal transduction was determined by assessing Fas, Fas-ligand (FasL), tumor necrosis factor-α (TNF-α), Bcl-2, survivin, caspase-3, and the terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay. Cell cycle proteins, Ki-67 (MIB-1), p16, p53, and p63, were studied by both immunohistochemical and Western blot analysis.
RESULTS: The patient population consisted of 12 (60%) women and 8 (40%) men with a mean age of 46 (range, 32-64) years.. All cases of myxoma were sporadic myxomas rather than familial. Clinical presentations included: asymptomatic (26%), dyspnea (44%), stroke (9%), chest pain (9%), and fever (11%). All myxomas were located in the left atrium. Pathological scores for inflammation, cellularity, hyaline, calcification, and thrombosis, were not related to myxoma location or clinical events. In cardiac myxoma, apoptosis documented by TUNEL (70.9%+17.6%) and the caspase-3 (66.5%+32.5%) final common pathway is characterized by the extrinsic Fas/Fas-L (positive stained 70.9%+19.2%; 26.0%+17.2%, respectively dependent pathway, but not the intrinsic TNF-α or Bcl-2 dependent pathways. On the other hand, survivin, which suppresses apoptosis and regulates cell division, was strongly expressed in the cytoplasm (65.5%+19.4%) and affected cell proliferation (Ki-67; 10.1%+8.9%) and cell death (p63; 49.5%+29.1%). The Western Blot analysis (Fas/Fas-L, TNF-α, p16, p53 p63, and caspase-3) of the cultured cardiac myxoma cells confirmed the immunochemical results.
CONCLUSION: Sporadic cardiac myxomas contain both extrinsic Fas/FasL dependent and survivin anti-apoptosis pathways that control cell cycles, with changes in Ki-67, p16, p53 and p63.
CLINICAL IMPLICATIONS: The pathogenesis of cardiac myxoma and may provide clues for treatment.
DISCLOSURE: Pao-Hsien Chu, None.